Pyridine → HCID 59015886, compound

HRID 968843Notes

Reaction equation

HRID 968843 reaction equation
[CH2:1]([O:3][C:4]([C:6]([CH3:21])([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][CH2:17][C:18]([OH:20])=O)=[CH:11][CH:10]=1)[CH3:7])=[O:5])[CH3:2].C(Cl)(=O)C(Cl)=[O:24].CS(O)(=O)=O.[CH2:33]([N:36]([CH2:38][C:39]1[CH:44]=[CH:43][C:42]([Cl:45])=[C:41]([Cl:46])[CH:40]=1)[NH2:37])CC.[N:47]1C=C[CH:50]=[CH:49][CH:48]=1>C(OCC)(=O)C.CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]([CH3:7])([O:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:15][CH2:16][CH2:17][C:18]([NH:37][N:36]([CH2:38][C:39]2[CH:44]=[CH:43][C:42]([Cl:45])=[C:41]([Cl:46])[CH:40]=2)[C:33]([NH:47][CH2:48][CH2:49][CH3:50])=[O:24])=[O:20])=[CH:13][CH:14]=1)[CH3:21])=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 23584129HCID 23584129, compoundHCID 87623821HCID 87623821, compound

Product 1

HCID 59015886HCID 59015886, compoundYield 85%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent4×

Procedure

To 4-[4-(1-Ethoxycarbonyl-1-methylethoxy)phenyl]-butyric acid (1.005 g, 3.41 mmol) in ethyl acetate (10 mL) at rt was added DMF (1 pipette drop), followed by oxalyl chloride (0.4 mL, 0.582 g, 4.58 mmol) dropwise over 3 min. The resulting solution was stirred for 30 min at rt, then concentrated to an oil. The oil was twice reconstituted into toluene (20 mL) and concentrated to an oil, then dissolved in ethyl acetate (3 mL). N-Propyl-1-(3,4-dichlorophenylmethyl)hydrazine methane-sulfonate (1.1458 g, 3.08 mmol) was suspended in ethyl acetate (10 mL) at 0° C., and pyridine (0.65 mL, 636 mg, 8.04 mmol) was added. The solution of acid chloride in ethyl acetate was then added dropwise over 2 min, and the resulting mixture stirred for 15 min at 0° C. The mixture was then diluted with ethyl acetate and washed with 1 N HCl (2×) followed by sat'd aq. NaCl. It was then dried (MgSO4), filtered and concentrated to an oil, which was chromatographed on silica gel (3:2 ethyl acetate:hexanes) to afford the title compound as an oil (1.4397 g, 85%): 1H NMR (DMSO-d6, 60° C.) δ 9.61 (s, 1 H), 7.50 (d, 1 H, J=8 Hz), 7.47 (d, 1 H, J=2 Hz), 7.23 (dd, 1 H, J=8, 2 Hz), 7.01 (d, 2 H, J=8.5 Hz), 6.71 (d, 2 H, J=8.5 Hz), 6.41 (br m, 1 H), 4.53 (br s, 2 H), 4.15 (q, 2 H. J=7 Hz), 3.00 (m, 2 H), 2.43 (m, 2 H), 2.09 (t, 2 H, J=7 Hz), 1.74 (m, 2 H), 1.48 (s, 6 H), 1.40 (m, 2 H), 0.81 (t, 3 H, J=7.5 Hz); 13C NMR (DMSO-d6) δ 174.0, 172.1, 158.1, 153.8, 140.4, 135.8, 131.4, 130.9, 130.6, 130.1, 129.7, 129.1, 119.5, 79.2, 61.6, 50.9, 42.3, 34.4, 33.5, 27.1, 25.7, 23.7, 14.6, 11.9; IR (CHCl3) 3457, 3008, 2876, 1727, 1673, 1509 cm−1; Anal. Calcd. for C27H35Cl2N3O5: C, 58.70; H, 6.39; N, 7.61. Found: C, 58.60; H, 6.49; N, 7.67.

Workup

  1. concentrationconcentrated to an oil
  2. concentrationconcentrated to an oil
  3. dissolutiondissolved in ethyl acetate (3 mL)
  4. stirringthe resulting mixture stirred for 15 min at 0° C
  5. washwashed with 1 N HCl (2×)
  6. dry with materialIt was then dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated to an oil, which
  9. customwas chromatographed on silica gel (3:2 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-37b17393432c427f8d8d4db7e6257eb6
Source dataset
uspto-grants-2007_12
Patent number
US07304062B2

Reaction notes

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